TY - JOUR
T1 - Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2
T2 - Prevention of reperfusion injury
AU - Bertini, Riccardo
AU - Allegretti, Marcello
AU - Bizzarri, Cinzia
AU - Moriconi, Alessio
AU - Locati, Massimo
AU - Zampella, Giuseppe
AU - Cervellera, Maria N.
AU - Di Cioccio, Vito
AU - Cesta, Maria C.
AU - Galliera, Emanuela
AU - Martinez, Fernando O.
AU - Di Bitondo, Rosa
AU - Troiani, Giulia
AU - Sabbatini, Vilma
AU - D'Anniballe, Gaetano
AU - Anacardio, Roberto
AU - Cutrin, Juan C.
AU - Cavalieri, Barbara
AU - Mainiero, Fabrizio
AU - Strippoli, Raffaele
AU - Villa, Pia
AU - Di Girolamo, Maria
AU - Martin, Franck
AU - Gentile, Marco
AU - Santoni, Angela
AU - Corda, Daniela
AU - Poli, Giuseppe
AU - Mantovani, Alberto
AU - Ghezzi, Pietro
AU - Colotta, Francesco
PY - 2004/8/10
Y1 - 2004/8/10
N2 - The chemokine CXC ligand 8 (CXCL8)/IL-8 and related agonists recruit and activate polymorphonuclear cells by binding the CXC chemokine receptor 1 (CXCR1) and CXCR2. Here we characterize the unique mode of action of a small-molecule inhibitor (Repertaxin) of CXCR1 and CXCR2. Structural and biochemical data are consistent with a noncompetitive allosteric mode of interaction between CXCR1 and Repertaxin, which, by locking CXCR1 in an inactive conformation, prevents signaling. Repertaxin is an effective inhibitor of polymorphonuclear cell recruitment in vivo and protects organs against reperfusion injury. Targeting the Repertaxin interaction site of CXCR1 represents a general strategy to modulate the activity of chemoattractant receptors.
AB - The chemokine CXC ligand 8 (CXCL8)/IL-8 and related agonists recruit and activate polymorphonuclear cells by binding the CXC chemokine receptor 1 (CXCR1) and CXCR2. Here we characterize the unique mode of action of a small-molecule inhibitor (Repertaxin) of CXCR1 and CXCR2. Structural and biochemical data are consistent with a noncompetitive allosteric mode of interaction between CXCR1 and Repertaxin, which, by locking CXCR1 in an inactive conformation, prevents signaling. Repertaxin is an effective inhibitor of polymorphonuclear cell recruitment in vivo and protects organs against reperfusion injury. Targeting the Repertaxin interaction site of CXCR1 represents a general strategy to modulate the activity of chemoattractant receptors.
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U2 - 10.1073/pnas.0402090101
DO - 10.1073/pnas.0402090101
M3 - Article
C2 - 15282370
AN - SCOPUS:4143050328
SN - 0027-8424
VL - 101
SP - 11791
EP - 11796
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 32
ER -